The promise of Precision Medicine in the United States can be most effectively realized on a large scale in the next decades if a research infrastructure is established and accessible to scientists across the nation and includes a large and engaged study population with comprehensive health and lifestyle histories linked to biospecimens and clinical data. Investigators from 4 integrated delivery networks (IDNs) spanning 7 states of the Health Care Systems Research Network (HCSRN, est. as HMORN in 1994), Henry Ford Health System and its partner Spectrum Health (HF-SH) in Michigan, Baylor Scott & White (BSW) in Texas, Essentia Health (EH) located in Minnesota, North Dakota, Wisconsin and Idaho, and Meyers-Fallon Primary Care Institute (MF) located in Massachusetts, have come together to form the PRECISION MEDICINE TRANS-AMERICA CONSORTIUM for the HCSRN (TACH) for the purpose of recruiting, enrolling and retaining 10,000 patient volunteers, herein designated as Patient Partners, into the Precision Medicine Initiative Cohort Program, at two of the sites in the initial 12 month period, with the potential to expand to even more HCSRN locations. The Precision Medicine Initiative (PMI) represents a major shift in the way research is conceptualized in the US. Rather than several small disease specific prospective studies, this major initiative develops the largest single prospective study involving patients and individuals with diverse sets of clinical histories, environmental exposures, demographics, genetic susceptibility, and beliefs about medical care. Furthermore, as opposed to researchers collecting data and restricting access to the outside scientific community, this study seeks to develop an open access structure whereby scientists can leverage the same data and infrastructure to make new discoveries and revolutionize medical care. Most importantly, this initiative seeks to engage participants as lifelong partners, such that by agreeing to share their data, Patient Partners will receive data and feedback on their own risk and protective factors for diseases. Finally, by combining all of these unique data sources, we can move towards tailoring treatments to patients. This, clearly, represents a new age of research, and our TACH network fully-supports and embraces this movement. We not only share the important philosophy of the NIH and the PMI, but have demonstrated this philosophy in our prior work. As we will describe, we have the resources, network, and experience to become a successful Regional Medical Center Healthcare Provider Organization (RMC-HPO) network in the PMI Cohort Program (PMI-CP). Our proposed TACH network draws upon the strengths of the HCSRN, a consortium of 18 large IDNs serving the vast majority of U.S. states. Our proposed network involves four HCSRN sites (HF-SH, BSW, EH, and MF). All participating HCSRN sites have a standard Virtual Data Warehouse (VDW), which has extensive clinical and demographic information for all members. This data infrastructure is extremely innovative for multisite studies. The VDW includes a combination of electronic health records (EHR) and insurance claims data, which allows the capture of nearly all health care utilization (~99%) within and outside of the system. Data on demographics, encounters, prescriptions, diagnoses, procedures, and enrollment are organized into uniform datasets using standardized variables and definitions across sites. The participating IDNs are all using the Epic EHR system, which is the largest and most commonly used EHR across the US ? over 52% of Americans now have an Epic health record. Epic employs a Care Everywhere feature, which allows systems to access EHR data from any Epic-using facility, with patient permission. All HCSRN sites are leading IDNs with affiliated health plans (Commercial, Medicaid, Medicare plans) and academic research centers. They have all collaborated for decades on multi-site research projects (see Past Performance Section), and are supported by federal infrastructure support, including (but not limited to) the NCI-funded Cancer Research Network (U24CA171524), NIMH-funded Mental Health Research Network (U19MH092201), Health Systems Node of the NIDA Clinical Trials Network (UG1DA040314), FDA-funded Mini-Sentinel, and NIA-funded AGING Initiative (R24AG045050), among many others. Populations vary by health system, but the demographic make-up is diverse and broadly representative of their local state?s general populations. Each site has experienced investigators, coordinators, informatics specialists, nurses, recruiters, medical and lab associates, statisticians, and other staff already in place and available to participate in the PMI-CP project immediately. This is essential, given that this project requires rapid recruitment and scale-up. The IDNs all manage many NIH projects, including numerous multi-site prospective studies and clinical trials. Over 100 multi-site trials and prospective studies have been externally funded across the HCSRN. As demonstrated in the ?Key Personnel Section,? investigators have vast expertise in a diverse range of disease areas (e.g., cardiovascular disease, cancer, diabetes, allergy, asthma, mental health, substance use, obesity, chronic pain, dementia) and research designs (e.g., experimental, prospective, case control, observational, and big-data EHR epidemiological studies) as well as in patient engagement, health informatics, and genetic research. All TACH sites employ NIH-funded investigators with extensive experience in recruiting and retaining sizeable numbers of research participants, in collecting biospecimens and self-report survey data, using electronic health record (EHR) data, e-consenting, coordinating multi-site data streams, and in collaborating with other health provider organizations and national centralized research cores. These IDN HPOs in the TACH network together provide comprehensive health services to over 9 million diverse patients each year. We will capitalize on our experience in recruiting and retaining large numbers of participants in epidemiological and clinical cohorts along with our patient-centered and process improvement approaches and expertise in managing multi-site EHR data, to efficiently maximize recruitment and retention, and foster true partnerships with the TACH PMI-CP Patient Partners, as well as nimbly identify and solve project problems as they arise, or make needed modifications.